Synthesis of deuterated aldehydes

A method for preparing a deuterated aldehyde of formula

• RZ—C(O)-D,
• wherein
• RZ is alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl;
• wherein the alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl are each optionally substituted with one or more Ra, and RZ is optionally deuterated;
• Ra at each occurrence is independently halogen, —CN, —OH, nitro, —O-benzyl, —NH(t-butoxycarbonyl), —NH(benzyloxycarbonyl), alkyl, alkenyl, alkynyl, alkoxy, —OC(O)-alkyl, —C(O)O-alkyl, —C(O)NH-alkyl, cycloalkyl, aryl, —O-aryl, —C(O)-aryl, heteroaryl, or heterocyclyl, wherein the alkyl, alkenyl, alkynyl, alkoxy, —OC(O)-alkyl, —C(O)O-alkyl, —C(O)NH-alkyl, cycloalkyl, aryl, —O-aryl, —C(O)-aryl, heteroaryl, or heterocyclyl is optionally substituted;
• and
• the level of deuterium incorporation of the —C(O)-D moiety is at least 90%;
• the method comprising:
• contacting an aldehyde of formula
• RZ′—C(O)—H
• with an N-heterocyclic carbene catalyst in a solvent comprising D2O, thereby producing the deuterated aldehyde,
• wherein RZ′ is alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl;
• wherein the alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl are each optionally substituted with one or more Rb;
• Rb at each occurrence is independently halogen, —CN, —OH, nitro, —O-benzyl, —NH(t-butoxycarbonyl), —NH(benzyloxycarbonyl), alkyl, alkenyl, alkynyl, alkoxy, —OC(O)-alkyl, —C(O)O-alkyl, —C(O)NH-alkyl, cycloalkyl, aryl, —O-aryl, —C(O)-aryl, heteroaryl, or heterocyclyl, wherein the alkyl, alkenyl, alkynyl, alkoxy, —OC(O)-alkyl, —C(O)O-alkyl, —C(O)NH-alkyl, cycloalkyl, aryl, —O-aryl, —C(O)-aryl, heteroaryl, or heterocyclyl is optionally substituted, and
• wherein the N-heterocyclic carbene catalyst is a compound of formula (I)
• wherein
• W is S or NRA;
• “-” in Q1-Q2 is a single bond, wherein
• Q1-Q2 is CRx1Ry1—CRx2Ry2;
• RA and RB are each independently an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, or an optionally substituted heterocyclyl;
• RC, and RD are each independently hydrogen, an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, or an optionally substituted heterocyclyl;
• RA and RC, RB and RD, and/or RC and RD alternatively together with the N or C atoms to which they are attached form a ring;
• RB alternatively is an alkylene forming a dimer;
• Rx1, Ry1, Rx2, and Ry2 are each independently hydrogen or alkyl;
• and
• X− is counter ion.